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| 10. |
- Amin, Kawa, et al.
(författare)
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Inflammation and structural changes in the airways of patients with atopicand nonatopic asthma : BHR group
- 2000
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 162:6, s. 2295-2301
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to compare the cellular pattern and structural changes in the airway walls of atopic and nonatopic patients with asthma. Bronchial biopsy specimens were obtained from 13 atopic subjects with asthma, nine nonatopic patients with asthma, and seven healthy control subjects and investigated using immunohistochemical methods. The number of eosinophils increased in both asthma groups, but significantly more in the atopic group. The number of mast cells increased similarly in the two asthma groups, whereas the number of neutrophils increased only in the nonatopic asthma group. The number of T-lymphocytes (CD3-, CD4-, CD8-, CD-25-positive cells) was higher in patients with atopic asthma compared with nonatopic asthma. Interleukin-4 (IL-4) and IL-5-positive cells were more frequently found in the atopic asthma group, whereas cells staining for IL-8 were more frequent in the nonatopic group. The degree of epithelial damage was significantly higher in the atopic asthma group compared with the control subjects and the nonatopic asthmatics. The tenascin and laminin layer was significantly thicker in the atopic group compared with the group of nonatopic asthmatics. In the atopic group, there was a significant negative correlation between epithelial integrity (defined as the relative length of intact epithelium) and the eosinophil count and also between the number of CD25-positive cells and epithelial integrity. The number of mast cells correlated positively with the thickness of tenascin- and laminin-positive layers. In conclusion, we provide evidence of different patterns of involvement of inflammatory cells in atopic and nonatopic patients with asthma. There were also structural differences in the bronchial mucous membrane between atopic asthma and nonatopic asthma. This suggests that there are differences in the extent of the immunopathologic response of these clinically distinct forms of asthma.
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| 15. |
- Askling, J, et al.
(författare)
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Increased risk for cancer following sarcoidosis
- 1999
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Ingår i: American journal of respiratory and critical care medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 160:55 Pt 1, s. 1668-1672
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Tidskriftsartikel (refereegranskat)
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| 16. |
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| 17. |
- Aurora, P., et al.
(författare)
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Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis
- 2005
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Ingår i: Am J Respir Crit Care Med. - 1073-449X. ; 171:3, s. 249-56
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Tidskriftsartikel (refereegranskat)abstract
- Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.
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| 19. |
- Azarbarzin, A., et al.
(författare)
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Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness
- 2022
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 206:6, s. 767-774
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (Delta HR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment Delta HR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: Delta HR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index >= 15 events/h] with Epworth Sleepiness Scale score, 10; n(CPAP):n(control) = 113:113; male, 85%; age, 66 +/- 8 [mean +/- SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by Delta HR (treatmentby-Delta HR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment Delta HR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in Delta HR; P, 0.05). This means that in patients with a Delta HR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P<0.05), but no significant risk reduction was estimated in patients with a mean Delta HR (6 beats/min; CPAP risk reduction, 16% [253% to 54%]; P= 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the Delta HR. Specifically, patients with higher Delta HR exhibit greater cardiovascular benefit from CPAP therapy.
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- Backman, Helena, et al.
(författare)
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Lung function trajectories and associated mortality among adults with and without airway obstruction
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:10, s. 1063-1074
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Spirometry is essential for diagnosis and assessment of prognosis in COPD.Objectives: To identify FEV1 trajectories and their determinants, based on annual spirometry measurements among individuals with and without airway obstruction. Furthermore, to assess mortality in relation to trajectories.Methods: In 2002-04, individuals with airway obstruction (AO) (FEV1/VC<0.70, n=993) and age- and sex-matched non-obstructive (NO) referents were recruited from population-based cohorts. Annual spirometries until 2014 were utilized in joint-survival Latent Class Mixed Models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up.Results: Three trajectories were identified among the AO-cases and two among the NO referents. Trajectory membership was driven by baseline FEV1%predicted (%pred) in both groups and additionaly, pack-years in AO and current smoking in NO. Longitudinal FEV1%pred level depended on baseline FEV1%pred, pack-years and obesity. The trajectories were distributed: 79.6% T1AO FEV1-high with normal decline, 12.8% T2AO FEV1-high with rapid decline, and 7.7% T3AO FEV1-low with normal decline (mean 27, 72 and 26 mL/year) among AO-individuals, and 96.7% T1NO FEV1-high with normal decline and 3.3% T2NO FEV1-high with rapid decline (mean 34 and 173 mL/year) among referents. Hazard for death was increased for T2AO (HR1.56) and T3AO (HR3.45) vs. T1AO, and for T2NO (HR2.99) vs. T1NO.Conclusions: Three different FEV1 trajectories were identified among those with airway obstruction and two among the referents, with different outcomes in terms of FEV1-decline and mortality. The FEV1 trajectories among airway obstructive and the relationship between low FVC and trajectory outcome are of particular clinical interest.
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- Bafadhel, Mona, et al.
(författare)
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Acute Exacerbations of Chronic Obstructive Pulmonary Disease : Identification of Biologic Clusters and Their Biomarkers
- 2011
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 184:6, s. 662-671
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1 beta, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83-0.95); serum CXCL10, 0.83 (95% CI, 0.70-0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78-0.93), respectively. Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1 beta, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
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| 26. |
- Bafadhel, Mona, et al.
(författare)
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Blood Eosinophils to Direct Corticosteroid Treatment of Exacerbations of Chronic Obstructive Pulmonary Disease A Randomized Placebo-Controlled Trial
- 2012
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 186:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Objectives: Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. Methods: Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and <= 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. Measurements and Main Results: There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). Conclusions: The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.
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| 31. |
- Batista Borges, João, 1966-
(författare)
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The Plausibility of "Bronchiolotrauma"
- 2018
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 197:8, s. 1086-1087
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Tidskriftsartikel (refereegranskat)
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| 32. |
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| 33. |
- Beeh, Kai M, et al.
(författare)
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How Do Dual Long-acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?
- 2017
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 196:2, s. 139-149
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Forskningsöversikt (refereegranskat)abstract
- Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease (COPD). Several studies have documented that long-acting bronchodilators (LABDs) can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroids (LABA/ICS) combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single LABDs or LABA/ICS in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. While preclinical studies suggest LABAs and LAMAs have anti-inflammatory effects, such effects have not been demonstrated yet in patients with COPD.
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- Bellani, Giacomo, et al.
(författare)
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Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study.
- 2017
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 195:1, s. 67-77
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse.Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful.Methods: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome.Measurements and Main Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg.Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg.
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| 38. |
- Betsuyaku, Tomoko, et al.
(författare)
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Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema
- 1999
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 159:6, s. 1985-1991
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Tidskriftsartikel (refereegranskat)abstract
- Evidence for the contribution of neutrophils to the pathogenesis of pulmonary emphysema is not convincing. We evaluated neutrophil involvement in subclinical pulmonary emphysema by measuring human neutrophil lipocalin (HNL) and two matrix metalloproteinases, gelatinase B (MMP-9) and neutrophil collagenase (MMP-8), in bronchoalveolar lavage fluid (BALF) from 65 community-based older volunteers. HNL is a recently isolated 24-kD protein secreted from secondary granules of activated neutrophils. Despite no appreciable increase in the number of neutrophils, the level of HNL was significantly increased in BALF from subjects with emphysema evidenced by computed tomography regardless of current smoking, as compared with smokers without emphysema. The levels of MMP-9 and MMP-8 were also significantly higher in current smokers with emphysema than in those without emphysema. The appearance of a 130-kD HNL/MMP-9 complex on gelatin zymography and HNL immunoblot indicated neutrophils to be a significant source of MMP-9 in the subjects' BALF. In a 24-h culture medium of alveolar macrophages, only a latent form of MMP-9 was detected, and there was no difference in the level of MMP-9 between the groups. These data provide further evidence for neutrophil involvement in subclinical pulmonary emphysema.
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| 42. |
- Blanc, P. D., et al.
(författare)
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The Occupational Burden of Nonmalignant Respiratory Diseases An Official American Thoracic Society and European Respiratory Society Statement
- 2019
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 199:11, s. 1312-1334
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases. RAHAM J L, 1986, Applied Pathology, V4, P138
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| 44. |
- Boner, A. L., et al.
(författare)
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Bronchial reactivity in asthmatic children at high and low altitude : Effect of budesonide
- 1995
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 151:4, s. 1194-1200
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Tidskriftsartikel (refereegranskat)abstract
- Inhaled steroids may control bronchial inflammation in asthmatics exposed to allergens. In this study we evaluated whether prophylactic budesonide would prevent relapse of asthma in children re-exposed to offending allergens at sea level, after a period of antigen avoidance at high altitude. Thirty children received either budesonide (200 micrograms b.i.d.) or placebo (double-blind). Following a 4-wk baseline period and 2 wk of treatment at high altitude, children were treated for 3 mo at sea level. Methacholine challenge and pulmonary function studies were performed before and after baseline period, after the 2 wk of treatment in the mountain environment, and at the end of treatment. ECP serum levels were evaluated after the baseline period and at the end of treatment. PEFR and symptoms were recorded in a diary card during the study. The increase in methacholine provocative dosage was greater, although not significant (p = 0.096), in the budesonide than in the placebo group after the treatment at high altitude and remained higher at the end of the treatment (p = 0.04). ECP levels increased in both the groups with no significant difference. Our results confirm that budesonide, in addition to its efficacy in treating pre-existent airway inflammation, is effective in preventing the increase of reactivity in asthmatic children re-exposed to allergens.
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| 45. |
- Borges, João Batista
(författare)
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Enlarging and protecting an aerated lung
- 2008
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 177:4, s. 463; author reply 463-464
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Tidskriftsartikel (refereegranskat)
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| 46. |
- Borges, João Batista, et al.
(författare)
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The Quest for the Holy Grail : A Dead Lock
- 2010
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 182:4, s. 579-580
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Tidskriftsartikel (refereegranskat)
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